Western Uganda is a key region for understanding the development of the western branch of the East African rift system and its interaction with pre-existing cratonic lithosphere. It is also the site of the topographically anomalous Rwenzori Mountains, which attain altitudes of >5000 m within the rift. New structural and geochronological data indicate that western Uganda south and east of the Rwenzori Mountains consists of a WSW to ENE trending fold and thrust belt emplaced by thick-skinned tectonics that thrust several slices of Proterozoic and Archaean units onto the craton from the south. The presence of Archaean units within the thrust stack is supported by new Laser-ICP-MS U-Pb age determinations (2637-2584 Ma) on zircons from the Rwenzori foothills. Repetition of the Paleoproterozoic units is confirmed by mapping the internal stratigraphy where a basal quartzite can be used as marker layer, and discrete thrust units show distinct metamorphic grades. The thrust belt is partially unconformably covered by a Neoproterozoic nappe correlated with the Kibaran orogenic belt. Even though conglomerates mark the bottom of the Kibaran unit, intensive brittle fault zones and pseudotachylites disprove an autochthonous position. The composition of volcanics in the Toro-Ankole field of western Uganda can be explained by the persistence of a cratonic lithosphere root beneath the northwardly thrusted Archaean and Palaeoproterozoic rocks of westernmost Uganda. Volcanic geochemistry indicates thinning of the lithosphere from >140 km beneath Toro-Ankole to ca. 80 km beneath the Virunga volcanic field about 150 km to the south. We conclude that the western branch of the East African rift system was initiated in an area of thinner lithosphere with Palaeoproterozoic cover in the Virunga area and has propagated northwards where it now abuts against thick cratonic lithosphere covered by a thrust belt consisting of gneisses, metasediments and metavolcanics of Neoarchaean to Proterozoic age.